tbuckley/cabot-search huggingface dataset:
Prefrontal engrams of long-term fear memory perpetuate pain perception
Authors: Alina Stegemann, Sheng Liu, Oscar Andrés Retana Romero, Manfred Josef Oswald, Yechao Han, Carlo Antonio Beretta, Zheng Gan, Linette Liqi Tan, William Wisden, Johannes Gräff, Rohini Kuner
Journal: Nature Neuroscience (2023)

Abstract A painful episode can lead to a life-long increase in an individual’s experience of pain. Fearful anticipation of imminent pain could play a role in this phenomenon, but the neurobiological underpinnings are unclear because fear can both suppress and enhance pain. Here, we show in mice that long-term associative fear memory stored in neuronal engrams in the prefrontal cortex determines whether a painful episode shapes pain experience later in life. Furthermore, under conditions of inflammatory and neuropathic pain, prefrontal fear engrams expand to encompass neurons representing nociception and tactile sensation, leading to pronounced changes in prefrontal connectivity to fear-relevant brain areas. Conversely, silencing prefrontal fear engrams reverses chronically established hyperalgesia and allodynia. These results reveal that a discrete subset of prefrontal cortex neurons can account for the debilitating comorbidity of fear and chronic pain and show that attenuating the fear memory of pain can alleviate chronic pain itself.
Validating the Breathing Vigilance Questionnaire for use in dysfunctional breathing
Authors: Jennifer Steinmann, Adam Lewis, Toby J. Ellmers, Mandy Jones, Vicky MacBean, Elmar Kal
Journal: European Respiratory Journal (2023)

Dysfunctional breathing is common among people with and without primary respiratory pathology. While anxiety can contribute to dysfunctional breathing, the underpinning mechanism is unclear. One explanation is that anxiety induces conscious, vigilant monitoring of breathing, disrupting "automatic" breathing mechanics. We validated a new tool that quantifies such breathing-related "vigilance": the Breathing Vigilance Questionnaire (Breathe-VQ).
Wnt7a deficit is associated with dysfunctional angiogenesis in pulmonary arterial hypertension
Authors: Ananya Chakraborty, Abinaya Nathan, Mark Orcholski, Stuti Agarwal, Elya A. Shamskhou, Natasha Auer, Ankita Mitra, Eleana Stephanie Guardado, Gowri Swaminathan, David F. Condon, Joyce Yu, Matthew McCarra, Nicholas H. Juul, Alden Mallory, Roberto A. Guzman-Hernandez, Ke Yuan, Vanesa Rojas, Joseph T. Crossno, Lai-Ming Yung, Paul B. Yu, Thomas Spencer, Robert A. Winn, Andrea Frump, Vijaya Karoor, Tim Lahm, Haley Hedlin, Jeffrey R. Fineman, Robert Lafyatis, Carsten N.F. Knutsen, Cristina M. Alvira, David N. Cornfield, Vinicio A. de Jesus Perez
Journal: European Respiratory Journal (2023)

Introduction: Pulmonary arterial hypertension (PAH) is characterised by loss of microvessels. The Wnt pathways control pulmonary angiogenesis but their role in PAH is incompletely understood. We hypothesised that Wnt activation in pulmonary microvascular endothelial cells (PMVECs) is required for pulmonary angiogenesis, and its loss contributes to PAH. Methods: Lung tissue and PMVECs from healthy and PAH patients were screened for Wnt production. Global and endothelial-specific Wnt7a −/– mice were generated and exposed to chronic hypoxia and Sugen-hypoxia (SuHx). Results: Healthy PMVECs demonstrated &gt;6-fold Wnt7a expression during angiogenesis that was absent in PAH PMVECs and lungs. Wnt7a expression correlated with the formation of tip cells, a migratory endothelial phenotype critical for angiogenesis. PAH PMVECs demonstrated reduced vascular endothelial growth factor (VEGF)-induced tip cell formation as evidenced by reduced filopodia formation and motility, which was partially rescued by recombinant Wnt7a. We discovered that Wnt7a promotes VEGF signalling by facilitating Y1175 tyrosine phosphorylation in vascular endothelial growth factor receptor 2 (VEGFR2) through receptor tyrosine kinase-like orphan receptor 2 (ROR2), a Wnt-specific receptor. We found that ROR2 knockdown mimics Wnt7a insufficiency and prevents recovery of tip cell formation with Wnt7a stimulation. While there was no difference between wild-type and endothelial-specific Wnt7a −/– mice under either chronic hypoxia or SuHx, global Wnt7a +/– mice in hypoxia demonstrated higher pulmonary pressures and severe right ventricular and lung vascular remodelling. Similar to PAH, Wnt7a +/– PMVECs exhibited an insufficient angiogenic response to VEGF-A that improved with Wnt7a. Conclusions: Wnt7a promotes VEGF signalling in lung PMVECs and its loss is associated with an insufficient VEGF-A angiogenic response. We propose that Wnt7a deficiency contributes to progressive small vessel loss in PAH.
Attitudes related to technology for active and healthy aging in a national multigenerational survey
Authors: J. Offerman, S. Fristedt, S. M. Schmidt, C. Lofqvist, S. Iwarsson
Journal: Nature Aging (2023)

Abstract Research is needed to understand attitudes toward and adoption of the broad range of technologies available to support active and healthy aging in different generations. The present article gives an overview of the GenerationTech survey and sample, and describes attitudes and acceptance related to technology in general and as a means to support active and healthy aging. A national survey was conducted with a random sample ( n = 2,121) including men and women from three generations (30–39, 50–59 and 70–79-year-olds) in Sweden. The generations shared some attitudes toward and acceptance of technologies for active and healthy aging. However, what kind of technologies are preferred to support active and healthy aging and the reasons for using certain technologies differed by generation. The findings could help guide the development and implementation of technologies for active and healthy aging throughout the aging process.
Acetylation of histone H2B marks active enhancers and predicts CBP/p300 target genes
Authors: Takeo Narita, Yoshiki Higashijima, Sinan Kilic, Tim Liebner, Jonas Walter, Chunaram Choudhary
Journal: Nature Genetics (2023)

Abstract Chromatin features are widely used for genome-scale mapping of enhancers. However, discriminating active enhancers from other cis -regulatory elements, predicting enhancer strength and identifying their target genes is challenging. Here we establish histone H2B N-terminus multisite lysine acetylation (H2BNTac) as a signature of active enhancers. H2BNTac prominently marks candidate active enhancers and a subset of promoters and discriminates them from ubiquitously active promoters. Two mechanisms underlie the distinct H2BNTac specificity: (1) unlike H3K27ac, H2BNTac is specifically catalyzed by CBP/p300; (2) H2A–H2B, but not H3–H4, are rapidly exchanged through transcription-induced nucleosome remodeling. H2BNTac-positive candidate enhancers show a high validation rate in orthogonal enhancer activity assays and a vast majority of endogenously active enhancers are marked by H2BNTac and H3K27ac. Notably, H2BNTac intensity predicts enhancer strength and outperforms current state-of-the-art models in predicting CBP/p300 target genes. These findings have broad implications for generating fine-grained enhancer maps and modeling CBP/p300-dependent gene regulation.
Flexible and efficient handling of nanopore sequencing signal data with slow5tools
Authors: Hiruna Samarakoon, James M. Ferguson, Sasha P. Jenner, Timothy G. Amos, Sri Parameswaran, Hasindu Gamaarachchi, Ira W. Deveson
Journal: Genome biology (2023)

Abstract Nanopore sequencing is being rapidly adopted in genomics. We recently developed SLOW5, a new file format with advantages for storage and analysis of raw signal data from nanopore experiments. Here we introduce slow5tools , an intuitive toolkit for handling nanopore data in SLOW5 format. Slow5tools enables lossless data conversion and a range of tools for interacting with SLOW5 files. Slow5tools uses multi-threading, multi-processing, and other engineering strategies to achieve fast data conversion and manipulation, including live FAST5-to-SLOW5 conversion during sequencing. We provide examples and benchmarking experiments to illustrate slow5tools usage, and describe the engineering principles underpinning its performance.
By deflating the lungs pulmonologists help the cardiologists. A literature review
Authors: N. Siafakas, A. Trachalaki
Journal: Pulmonology (2023)

In this review, we present the effects of lung hyperinflation on the cardiovascular system (CVS) and the beneficial outcomes of different deflation treatment modalities. We discuss the effects of long-acting bronchodilator drugs, medical and surgical lung volume reduction on the performance of the CVS. Although there is a small number of studies investigating lung deflation and the CVS, the short-term improvement in heart function was clearly demonstrated. However, more studies, with longer duration, are needed to verify these significant beneficial effects of deflation of the lungs on the CVS. Dynamic hyperinflation during exercise could be a research model to investigate further the effects of lung hyperinflation and/or deflation on the CVS.
Endotypes in bronchiectasis: moving towards precision medicine. A narrative review
Authors: M. Martins, H.R. Keir, J.D. Chalmers
Journal: Pulmonology (2023)

Bronchiectasis is a highly complex entity that can be very challenging to investigate and manage. Patients are diverse in their aetiology, symptoms, risk of complications and outcomes. "Endotypes"- subtypes of disease with distinct biological mechanisms, has been proposed as a means of better managing bronchiectasis. This review discusses the emerging field of endotyping in bronchiectasis. We searched PubMed and Google Scholar for randomized controlled trials (RCT), observational studies, systematic reviews and meta-analysis published from inception until October 2022, using the terms: "bronchiectasis", "endotypes", "biomarkers", "microbiome" and "inflammation". Exclusion criteria included commentaries and non-English language articles as well as case reports. Duplicate articles between databases were initially identified and appropriately excluded. Studies identified suggest that it is possible to classify bronchiectasis patients into multiple endotypes deriving from their co-morbidities or underlying causes to complex infective or inflammatory endotypes. Specific biomarkers closely related to a particular endotype might be used to determine response to treatment and prognosis. The most clearly defined examples of endotypes in bronchiectasis are the underlying causes such as immunodeficiency or allergic bronchopulmonary aspergillosis where the underlying causes are clearly related to a specific treatment. The heterogeneity of bronchiectasis extends, however, far beyond aetiology and it is now possible to identify subtypes of disease based on inflammatory mechanisms such airway neutrophil extracellular traps and eosinophilia. In future biomarkers of host response and infection, including the microbiome may be useful to guide treatments and to increase the success of randomized trials. Advances in the understanding the inflammatory pathways, microbiome, and genetics in bronchiectasis are key to move towards a personalized medicine in bronchiectasis.
COPD treatment – a conceptual review based on critical endpoints
Authors: A. Roque, L. Taborda-Barata, Á.A. Cruz, G. Viegi, T. Maricoto
Journal: Pulmonology (2023)

Chronic obstructive pulmonary disease (COPD) is one of the main causes of death and disability worldwide. Many treatment options are now available, but criteria for choosing inhaled bronchodilators and inhaled corticosteroids have been under discussion. New trials have highlighted the role of patient`s characteristics, such as eosinophil count and exacerbation history, in selecting the most effective personalised treatment option. In this conceptual review, an in-depth rationale is developed with an integrative approach to COPD treatment, gathering data from the main clinical trials performed so far and that may provide support for actual GOLD 2023 recommendations. According to the patient's characteristics and profile, different treatment options, including mono, dual and triple therapies, are presented in a diagram matrix, comparing their efficacy in terms of reduction of exacerbations and mortality risk. Eosinophil counts and past exacerbation profile may play equally relevant roles to predict the individual risk and the potential response to inhaled corticosteroids. Thus, a comprehensive approach considering these two predictors is needed to aid clinicians decide preventative actions and choice of a first-line or step-up treatment.
What role for somatic mutations in systemic inflammatory and autoimmune diseases associated with myelodysplastic neoplasms and chronic myelomonocytic leukemias?
Authors: Lin-Pierre Zhao, Marie Sébert, Arsène Mékinian, Olivier Fain, Marion Espéli, Karl Balabanian, Nicolas Dulphy, Lionel Adès, Pierre Fenaux
Journal: Leukemia (2023)
Re: Michael S. Leapman, Cassandra L. Thiel, Ilyssa O. Gordon, et al. Environmental Impact of Prostate Magnetic Resonance Imaging and Transrectal Ultrasound Guided Prostate Biopsy. Eur Urol. 2023;83:463–71
Authors: Fabian Daza, Cesar Díaz Ritter, Nicolas Badillo
Journal: European Urology (2023)
Author Correction: PCYT2-regulated lipid biosynthesis is critical to muscle health and ageing
Authors: Domagoj Cikes, Kareem Elsayad, Erdinc Sezgin, Erika Koitai, Ferenc Torma, Michael Orthofer, Rebecca Yarwood, Leonhard X. Heinz, Vitaly Sedlyarov, Nasser Darwish Miranda, Adrian Taylor, Sophie Grapentine, Fathiya al-Murshedi, Anne Abot, Adelheid Weidinger, Candice Kutchukian, Colline Sanchez, Shane J. F. Cronin, Maria Novatchkova, Anoop Kavirayani, Thomas Schuetz, Bernhard Haubner, Lisa Haas, Astrid Hagelkruys, Suzanne Jackowski, Andrey V. Kozlov, Vincent Jacquemond, Claude Knauf, Giulio Superti-Furga, Eric Rullman, Thomas Gustafsson, John McDermot, Martin Lowe, Zsolt Radak, Jeffrey S. Chamberlain, Marica Bakovic, Siddharth Banka, Josef M. Penninger
Journal: Nature Metabolism (2023)
Identification of cell barcodes from long-read single-cell RNA-seq with BLAZE
Authors: Yupei You, Yair D. J. Prawer, Ricardo De Paoli-Iseppi, Cameron P. J. Hunt, Clare L. Parish, Heejung Shim, Michael B. Clark
Journal: Genome biology (2023)

Long-read single-cell RNA sequencing (scRNA-seq) enables the quantification of RNA isoforms in individual cells. However, long-read scRNA-seq using the Oxford Nanopore platform has largely relied upon matched short-read data to identify cell barcodes. We introduce BLAZE, which accurately and efficiently identifies 10x cell barcodes using only nanopore long-read scRNA-seq data. BLAZE outperforms the existing tools and provides an accurate representation of the cells present in long-read scRNA-seq when compared to matched short reads. BLAZE simplifies long-read scRNA-seq while improving the results, is compatible with downstream tools accepting a cell barcode file, and is available at https://github.com/shimlab/BLAZE .
The tumor ecosystem in head and neck squamous cell carcinoma and advances in ecotherapy
Authors: Yingying Gong, Lisha Bao, Tong Xu, Xiaofen Yi, Jinming Chen, Shanshan Wang, Zongfu Pan, Ping Huang, Minghua Ge
Journal: Molecular Cancer (2023)

Abstract The development of head and neck squamous cell carcinoma (HNSCC) is a multi-step process, and its survival depends on a complex tumor ecosystem, which not only promotes tumor growth but also helps to protect tumor cells from immune surveillance. With the advances of existing technologies and emerging models for ecosystem research, the evidence for cell-cell interplay is increasing. Herein, we discuss the recent advances in understanding the interaction between tumor cells, the major components of the HNSCC tumor ecosystem, and summarize the mechanisms of how biological and abiotic factors affect the tumor ecosystem. In addition, we review the emerging ecological treatment strategy for HNSCC based on existing studies.
The Increase in Hemoglobin Concentration With Altitude Differs Between World Regions and Is Less in Children Than in Adults
Authors: Heimo Mairbäurl, Samuel Kilian, Svenja Seide, Martina U. Muckenthaler, Max Gassmann, Rukundo K. Benedict
Journal: HemaSphere (2023)

To compensate for decreased oxygen partial pressure, high-altitude residents increase hemoglobin concentrations [Hb]. The elevation varies between world regions, posing problems in defining cutoff values for anemia or polycythemia. The currently used altitude adjustments (World Health Organization [WHO]), however, do not account for regional differences. Data from The Demographic and Health Survey (DHS) Program were analyzed from 32 countries harboring &gt;4% of residents at altitudes above 1000 m. [Hb]-increase, (ΔHb/km altitude) was calculated by linear regression analysis. Tables show 95% reference intervals (RIs) for different altitude ranges, world regions, and age groups. The prevalence of anemia and polycythemia was calculated using regressions in comparison to WHO adjustments. The most pronounced Δ[Hb]/km was found in East Africans and South Americans while [Hb] increased least in South/South-East Asia. In African regions and Middle East, [Hb] was decreased in some altitude regions showing inconsistent changes in different age groups. Of note, in all regions, the Δ[Hb]/km was lower in children than in adults, and in the Middle East, it was even negative. Overall, the Δ[Hb]/km from our analysis differed from the region-independent adjustments currently suggested by the WHO resulting in a lower anemia prevalence at very high altitudes. The distinct patterns of Δ[Hb] with altitude in residents from different world regions imply that one single, region-independent correction factor for altitude is not be applicable for diagnosing abnormal [Hb]. Therefore, we provide regression coefficients and reference-tables that are specific for world regions and altitude ranges to improve diagnosing abnormal [Hb].
The Tip60/Ep400 chromatin remodeling complex impacts basic cellular functions in cranial neural crest-derived tissue during early orofacial development
Authors: Sebastian Gehlen-Breitbach, Theresa Schmid, Franziska Fröb, Gabriele Rodrian, Matthias Weider, Michael Wegner, Lina Gölz
Journal: International Journal of Oral Science (2023)

Abstract The cranial neural crest plays a fundamental role in orofacial development and morphogenesis. Accordingly, mutations with impact on the cranial neural crest and its development lead to orofacial malformations such as cleft lip and palate. As a pluripotent and dynamic cell population, the cranial neural crest undergoes vast transcriptional and epigenomic alterations throughout the formation of facial structures pointing to an essential role of factors regulating chromatin state or transcription levels. Using CRISPR/Cas9-guided genome editing and conditional mutagenesis in the mouse, we here show that inactivation of Kat5 or Ep400 as the two essential enzymatic subunits of the Tip60/Ep400 chromatin remodeling complex severely affects carbohydrate and amino acid metabolism in cranial neural crest cells. The resulting decrease in protein synthesis, proliferation and survival leads to a drastic reduction of cranial neural crest cells early in fetal development and a loss of most facial structures in the absence of either protein. Following heterozygous loss of Kat5 in neural crest cells palatogenesis was impaired. These findings point to a decisive role of the Tip60/Ep400 chromatin remodeling complex in facial morphogenesis and lead us to conclude that the orofacial clefting observed in patients with heterozygous KAT5 missense mutations is at least in part due to disturbances in the cranial neural crest.
Identifying Early Infections in the Setting of CRS With Routine and Exploratory Serum Proteomics and the HT10 Score Following CD19 CAR-T for Relapsed/Refractory B-NHL
Authors: Kai Rejeski, Viktoria Blumenberg, Gloria Iacoboni, Lucia Lopez-Corral, Soraya Kharboutli, Rafael Hernani, Agnese Petrera, Niklas Müller, Friederike Hildebrand, Lisa Frölich, Philipp Karschnia, Christian Schmidt, David M. Cordas dos Santos, José Luis Piñana, Fabian Müller, Ana Africa Martin, Martin Dreyling, Michael von Bergwelt-Baildon, Pere Barba, Marion Subklewe, Veit L. Bücklein
Journal: HemaSphere (2023)

Early fever after chimeric antigen receptor T-cell (CAR-T) therapy can reflect both an infection or cytokine release syndrome (CRS). Identifying early infections in the setting of CRS and neutropenia represents an unresolved clinical challenge. In this retrospective observational analysis, early fever events (day 0-30) were characterized as infection versus CRS in 62 patients treated with standard-of-care CD19.CAR-T for relapsed/refractory B-cell non-Hodgkin lymphoma. Routine serum inflammatory markers (C-reactive protein [CRP], interleukin-6 [IL-6], procalcitonin [PCT]) were recorded daily. Exploratory plasma proteomics were performed longitudinally in 52 patients using a multiplex proximity extension assay (Olink proteomics). Compared with the CRS
Targeted therapy for cisplatin‐resistant lung cancer via aptamer‐guided nano‐zinc carriers containing USP14 siRNA
Authors: Xinmin Zhao, Xianghua Wu, Huijie Wang, Songtao Lai, Jialei Wang
Journal: MedComm (2023)

Cisplatin (DDP) is a common therapeutic option for non-small cell lung carcinoma (NSCLC). However, some patients fail to respond to the DDP chemotherapy. Therefore, identifying novel biomarkers to improve the diagnosis and treatment of NSCLC is important. Ubiquitin-specific protease (USP14) is involved in various pathological conditions including cancer; however, the role of USP14 in NSCLC remains elusive. The SELEX technology was used to identify aptamers that specifically recognize DDP-resistant lung cancer cells and couple them with nano-zinc (zinc hydroxide, Zn(OH)2) carriers. USP14 levels were higher in DDP-resistant lung cancer compared to DDP-sensitive lung cancer. The survival rate of lung cancer patients with increased USP14 expression was significantly lower than the survival rate of patients with low USP14 expression. Silencing USP14 increased the tumor antagonistic action of DDP in A549 cisplatin-resistant (A549/DDP) cells, while USP14 overexpression decreased the antagonist effects. Aptamer-targeted nano-zinc carriers were loaded with USP14 siRNA to target DDP-resistant lung cancer cells. Aptamer-targeted nano-zinc carriers containing USP14 siRNA increased the antitumor effects of DDP in A549/DDP cells and mice bearing A549/DDP cells. These results indicate that aptamer-guided nano-zinc carriers may be a potent carrier for the precise treatment of drug-resistant tumors.
Emerging roles of SARS-CoV-2 Spike-ACE2 in immune evasion and pathogenesis
Authors: Cosima T. Baldari, Anna Onnis, Emanuele Andreano, Giuseppe Del Giudice, Rino Rappuoli
Journal: Trends in Immunology (2023)

The COVID-19 pandemic, caused by SARS-CoV-2, has caused an estimated 5 billion infections and 20 million deaths by respiratory failure. In addition to the respiratory disease, SARS-CoV-2 infection has been associated with many extrapulmonary complications not easily explainable by the respiratory infection. A recent study showed that the SARS-CoV-2 spike protein, which mediates cell entry by binding to the angiotensin-converting enzyme 2 (ACE2) receptor, signals through ACE2 to change host cell behavior. In CD8+ T cells, spike-dependent ACE2-mediated signaling suppresses immunological synapse (IS) formation and impairs their killing ability, leading to immune escape of virus-infected cells. In this opinion article, we discuss the consequences of ACE2 signaling on the immune response and propose that it contributes to the extrapulmonary manifestations of COVID-19.
Society News
Journal: Neuro-Oncology (2023)

Journal Article Society News Get access Neuro-Oncology, Volume 25, Issue 4, April 2023, Page 811, https://doi.org/10.1093/neuonc/noad041 Published: 06 April 2023 Article history Corrected and typeset: 06 April 2023 Published: 06 April 2023